Fruity flavored nasal decongestant composition

ABSTRACT

An aqueous, flavored, topical, nasal decongestant composition containing an amount of oxymetazoline or a pharmaceutically acceptable salt thereof, e.g., oxymetazoline HCl sufficient to effect nasal decongestion and an amount of a fruity flavor e.g. cherry flavor, sufficient to mask the medicinal after-taste of the composition, together with an aqueous carrier.

BACKGROUND

This invention relates to an aqueous, flavored, topical, nasaldecongestant composition containing doxymetazoline or a pharmaceuticallyacceptable salt thereof, an aqueous carrier and sufficient fruity flavorto mask the medicinal after-taste of the composition.

Aqueous, topical, nasal decongestant compositions containingoxymetazoline hydrochloride, the longest acting nasal decongestantcurrently available, are applied to the nasal passages of mammalsespecially human beings to affect temporary relief of nasal congestionassociated with colds, hay fever and sinusitis. Menthol flavored nasaldecongestant compositions containing vapors of menthol, eucalyptol andcamphor and polysorbate in addition to oxymetazoline hydrochloride andan aqueous carrier are available as OTC products under the tradenameAFRIN® nasal spray from Schering Corporation, Kenilworth, New Jersey.However, such menthol flavored or unflavored nasal decongestantcomposition when applied to the nasal passages, causes a bittermedicinal after-taste.

T. M. Berman (New England Journal of Medicine, Aug. 23, 1979, Vol. 301,p 437) discloses addition of peppermint flavor to improve the taste oflidocaine used to anesthetize the pharynx and nasal passage beforebronchoscopy. D. E. Hornung et al. (Ann N.Y. Acad. Sci., 1987, Vol. 510,pp 86-90) discloses smell-taste perception in general terms. Neitherreference discloses or suggests the present invention.

SUMMARY OF THE INVENTION

We have surprisingly discovered that addition of small amounts of fruityflavors to aqueous topical nasal decongestant compositions containingoxymetazoline hydrochloride in an aqueous base effectively masks themedicinal after-taste of the decongestant composition. Accordingly, thepresent invention provides an aqueous, flavored, topical nasal,decongestant composition comprising an amount of oxymetazoline or apharmaceutically acceptable salt thereof sufficient to effect nasaldecongestion and an aqueous carrier and an amount of a fruity flavorsufficient to mask the medicinal after-taste of the topical nasaldecongestant composition. The present invention also provides anaqueous, flavored, topical nasal decongestant composition comprising anamount of oxymetazoline or a pharmaceutically acceptable salt thereofsufficient to effect nasal decongestion and an aqueous carriercontaining:

about 4.0 to about 7.0% by weight of 70% (w/v) sorbitol solution;

about 0 to about 0.025% by weight of at least one antimicrobialpreservative;

about 0.005 to about 0.5% by weight of a fruity flavor, and an amount ofa pharmaceutically acceptable base and buffer sufficient to maintain thepH of the composition within the range of about 4.0 to about 6.5, andwater. The present invention further provides a method of treating nasalcongestion by administering to a nasal passage of a patient with nasalcongestion an aqueous, fruity-flavored, topical nasal decongestantcomposition of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The fruity flavors found suitable for use in the present inventioninclude cherry, strawberry, peach and vanillin all of which are flavorsapproved for use in drugs by the United States FDA. The amount of fruityflavor found sufficient to mask the medicinal after-taste of the topicalnasal decongestant compositions of the present invention is within therange of about 0.005 to about 0.5% by weight of the composition. Theranges for individual fruity flavors are given in the table below.

    ______________________________________                                                   Concentration Range                                                                      Percent by Weight of                                    Fruity Flavor                                                                              mg/mL    Composition                                             ______________________________________                                        Cherry       0.1-4.0  0.0-1 to 0.4                                            Strawberry   0.05-5   0.005 to 0.5                                            Peach        0.1-3     0.01 to 0.3                                            Vanillin     0.1-3     0.01 to 0.3                                            ______________________________________                                    

The use of cherry flavor (preferably about 3.5 mg/mL) or strawberry(preferably about 4.0 mg/mL) in the compositions and methods of thepresent invention is preferred.

The amount of oxymetazoline or pharmaceutically acceptable salt thereoffound sufficient to effect nasal decongestion is in the range of about0.01% to about 0.1% by weight of the topical nasal decongestantcomposition. Typically, 0.025% by weight oxymetrazoline (as the HCI) issuitable for children 2 to 5 years of age and 0.05% by weight ofoxymethazoline (also as the HCI salt) is suitable for adults andchildren above five years of age. Oxymetazoline HCI is commerciallyavailable from Schering Labs, Kenilworth New Jersey. See also The MerckIndex, Tenth Edition, 1983 p. 6838. By the term "pharmaceuticallyacceptable salt" as used herein is meant the acid addition salt formedby admixing oxymetazoline with a pharmaceutically acceptable acid suchas HCl, HF, H₂ SO₄, HNO₃, malonic, succinic, trifluoroacetic acids andthe like.

The compositions of the present invention contains at least oneantimicrobial preservative in the range of 0% to about 0.025% by weightof the composition. Typical suitable preservatives function asantimicrobial agents and include the commercially availablepreservatives, e.g. phenyl mercuric acetate in the range of about 0 toabout 0.005% by weight, benzalkonium chloride in the range of about 0 toabout 0.02% by weight or thimerosal in the range of about 0.001 to about0.01% by weight.

The compositions of the present invention contain a sorbitol solution(70% w/v) normally present in the range of about 4.0 to 7.0% by weight.Sorbitol solution is a tonicity agent which renders the composition ofthe present invention isontonic with the body's fluids. Otherconcentrations of sorbitol and other tonicity agents well known to thoseskilled in the art are comtemplated to be within the scope of thisinvention.

The compositions of the present invention also include pharmaceuticallyacceptable buffers and pharmaceutically acceptable bases sufficient toadjust and maintain the pH of the compositions of the present inventionin the range of about 4.0 to about 6.5, preferably about 5.5 to about6.5. Typically suitable buffers include citrate, phosphate and glycine.Typically suitable bases include alkali metal hydroxides, especiallyNaOH.

The compositions of the present invention may be formulated for use byadults or children in the form of nose drops, or spray. A spray pump orplastic squeeze bottle may be use for the spray. The dosage andadministration regimen of Schering Corporation AFRIN® nasal spray in the1988 edition of the PDR for NON-PRESCRIPTION DRUGS at page 685 may befollowed.

EXAMPLE 1 Adult Strength Flavored Product

    ______________________________________                                                          Concentration                                               Ingredient          mg/mL    % by wgt.                                        ______________________________________                                        Oxymetazoline HCl   0.50     .05                                              Phenylmercuric Acetate                                                                            0.02     .002                                             Benzalkonium Chloride                                                                             0.20     .02                                              Glycine             3.754    .3754                                            70% (w/v) Sorbitol Solution                                                                       57.143   5.7143                                           Cherry Flavor       3.5      .35                                              Sodium Hydroxide to adjust                                                                        --       --                                               pH to within range of 5.5 to 6.5                                              Water Purified USP  q.s to 1 mL                                               ______________________________________                                    

METHOD OF PREPARATION

(1) Dissolve the oxymetazoline HCl, phenyl mercuric acetate,benzalkonium chloride, glycine, 70% (w/v) sorbitol solution, and cherryflavor into a volume of purified water sufficient to provide ahomogeneous solution. Adjust the pH of the so-formed solution to 5.5 to6.5 using a sodium hydroxide solution. Add sufficient purified water tothe final volume (1 mL) having the ingredient concentrations listedabove. Filter the solution.

Strawberry (4 mg/mL) may be substituted for cherry flavor in the aboveformulation.

Fill into 15 or 30 mL plastic squeeze bottles or 15 mL pump spraybottles or 20 mL dropper bottles.

EXAMPLE 2 Children's Strength Flavored Product

Follow the procedure of Example 1 but use 0.25 mg/mL of oxymetazolineHCl in the formulation instead of 0.50 mg/ml.

EXAMPLE 3 Exemplary Formulations

    ______________________________________                                                          Concentration Range                                         Ingredients         mg/mL     % by wgt.                                       ______________________________________                                        Oxymetazoline       0.01-0.1   0.001-0.01                                     Phenylmercuric acetate                                                                               0-0.05    0-0.005                                      Benzalkonium Chloride                                                                               0-0.2      0-0.02                                       70% (w/v) Sorbitol Solution                                                                         40-70    4.0-7.0                                        Fruity Flavor       0.05-5    0.005-0.5                                       Buffer and NaOH sufficient to adjust                                          and maintain pH in the range of                                               5.5 to 6.5                                                                    Water               q.s to 1 ml                                               ______________________________________                                    

The composition of Example 1 in the form of a nasal spray was tested andfound to have no medicinal after-taste.

What is claimed is:
 1. A method of masking the medicinal after-taste ofa nasally-applied oxymetazoline-containing decongestant compositionwhich comprises nasally applying an aqueous, flavored, topical nasaldecongestant composition comprising (1) an amount of oxymetazoline or apharmaceutically acceptable salt thereof sufficient to effect nasaldecongestion, (2) an aqueous carrier containing an amount of a fruityflavor sufficient to mask the medicinal after-taste of the topical nasaldecongestant composition.
 2. The method of claim 1 wherein the fruityflavor is cherry or strawberry.
 3. A method of masking the medicinalafter-taste of a nasally-applied oxymetazoline-containing decongestantcomposition which comprises nasally administering an aqueous, flavored,topical, nasal decongestant composition comprising (1) an amount oroxymetazoline of a pharmaceutically acceptable salt thereof sufficientto effect nasal decongestion and (2) an aqueous carrier containing:about4.0 to about 7.0% by weight of sorbitol; about 0 to about 0.25% byweight of at least one antimicrobial preservative; about 0.005 to about0.5% by weight of a fruity flavor, and (3) an amount of apharmaceutically acceptable base and buffer sufficient to maintain thepH of the composition within the range of about 4.0 to about 6.5; and(4) water.
 4. The method of claim 3 wherein the oxymetazoline HClcomprises about 0.01 to about 0.1% by weight of the composition.
 5. Themethod of claim 3 wherein the aqueous, flavored, topical, nasaldecongestant composition consists essentially of:

    ______________________________________                                                          Concentration                                               Ingredients       mg/mL                                                       ______________________________________                                        Oxymetazoline HCl 0.50                                                        Phenylmercuric Acetate                                                                          0.02                                                        Glycine           3.754                                                       70% (w/v) Sorbitol Solution                                                                     57.143                                                      Benzalkonium Chloride                                                                           0.20                                                        Fruity Flavor     0.05 to 5                                                   Sodium Hydroxide to adjust                                                                      --                                                          the pH to 5.5 to 6.5                                                          Water             q.s to make 1 mL                                            ______________________________________                                    


6. The method of claim 5 wherein the nasal decongestant contains 3.5mg/mL of cherry flavor.
 7. The method of claim 6 wherein the nasaldecongestant contains 4 mg/mL of strawberry flavor.
 8. A method oftreating nasal congestion which comprises administering to a nasalpassage of a patient with nasal congestion an aqueous, flavored,topical, nasal decongestant composition of claim
 1. 9. The method ofclaim 8 wherein said nasal decongestant composition is administered as aspray via a squeeze bottle.
 10. The method of claim 8 wherein said nasaldecongestant composition is administered as a spray via a spray pumpbottle.